Working with a contract development and manufacturing organization (CDMO) is a great way for smaller or diversified biotech companies, and even Big Pharma, to expand operations or modalities to reach the patients more efficiently. Outsourcing process development and manufacturing requires a lesser upfront investment with faster timelines while allowing teams at advanced therapy developers to focus on innovation. However, this relationship can deeply impact the quality and efficacy of a product. This article explores the balancing act of ensuring regulatory compliance via internal procedures at a CDMO and what to consider when starting
this relationship.

CDMOs will always have multiple customers, as this is how their business model is built. It can be an uncomfortable position to seek a CDMO, particularly for those coming from Big Pharma, where there is direct quality oversight over processes. Looking for a CDMO with a wide platform of tools that can be tailored to meet regulatory compliance and both provider and customer pharmaceutical quality system (PQS) requirements is important.

Unfortunately, many CDMOs offer quality processes with minimal flexibility for customers because this is the easiest for the CDMO to control. Doing this minimizes the risks associated with customer specific variations to processes, reduces costs for the CDMO, and is easier to defend during inspections. However, this can lead to a disconnect between the customer and the supplier.

When CDMOs develop quality agreements with a greater focus on client needs, it can increase trust, compliance, and even make audits easier to manage. Complex procedures can be simplified by engaging all parties and clearly documenting in the quality agreement from the start. While this may add initial time and cost, over the long run this will pay out with less process issues, including errors or oversights.

A CDMO should ask a lot of questions and take a consultative approach to building the quality agreement. Take a close look at their platform and internal quality standards and how this aligns with the needs of a product. Set the expectations out clearly, including defining the roles and responsibilities for the CDMO and customer. The agreement will clarify when and how to incorporate customer specific requirements and identify any areas for risk to address from the start.

Ensure that during this stage, and throughout the relationship, there is always open and honest dialogue about every detail. For instance, what is considered a repetitive deviation and when does a customer feel the need to sign off on it. The customer may define the second occurrence of an event as repetitive, while the CDMO might define it as the third occurrence.

When referring to this article, please cite it as McHee, I. Ensuring Quality in Contracted Support. 

BioPharm International Partnerships for Outsourcing

Articles

Quality

This article looks at the relationship between a CDMO quality organization and the client.

Ensuring Quality in Contracted Support

Drug development companies (sponsors) may assume a commitment to quality is inherent in the operations of every contract development and manufacturing organization (CDMO), simply because product quality is essential for ensuring patient safety. Certainly, every CDMO professes its commitment to quality. So, in evaluating potential partners to manufacture a drug or biologic, how can one accurately assess the CDMO’s commitment to quality?

The answer involves conducting a thorough on-site quality audit, asking the right questions, and requesting detailed information. The answers, data, and documents provided will reveal—by what they contain and what they omit—whether or not the CDMO has a strong quality management system and quality culture.

A CDMO should welcome an on-site audit of its facilities and operations as part of the vetting process. Reluctance to have an audit is a red flag that something is wrong.

If the sponsor company is a small start-up or has limited auditing experience, an experienced firm may be hired to conduct the inspection, ideally with the participation of a member of the sponsor’s own team.

If the sponsor conducts the inspection, a great way to ensure all the bases are covered is to follow the FDA quality system inspection technique that the agency publishes for use by its own inspectors (1). The FDA guide describes how inspections should be performed on six systems—those related to quality, facilities and equipment, materials, production, packaging and labeling, and laboratory controls. The approach described should be adopted, and the following key questions should be asked and certain information requested.

When referring to this article, please cite it as Szymanska, A. How to Evaluate a CDMO's Commitment to Quality. 

What do you need to ask during the vetting and selection process to ensure your clinical or commercial program won’t be derailed by a quality-related problem? 

How to Evaluate a CDMO’s Commitment to Quality

To reduce costs and streamline their internal processes, bio/pharmaceutical and biotech companies are increasingly outsourcing many of their internal operations related to the development of their therapeutic compounds, including preclinical testing. That said, contract research organizations (CROs) are playing a more important role in providing critical testing services required for internal validation purposes and submission to regulatory agencies. Navigating the preclinical testing process can be a somewhat confusing, if not difficult, task including identifying the proper partner for conducting the necessary studies to help advance a promising lead compound from the discovery phase to the initiation of investigational new drug (IND) process.

This article will serve as a useful guide, including why/when to outsource preclinical testing, the advantages and disadvantages of outsourcing this testing, and how to effectively choose a partner to conduct this testing.

With the ever-growing complexity of pharmaceutical therapeutic development, it is becoming more and more difficult for companies, both small start-ups and even large global entities, to maintain all the relevant capabilities internally required for full development of promising lead compounds to the initiation of the clinical testing phase. Academic institutions often collaborate with companies on early stage R&D with later-stage testing and manufacturing being outsourced to CROs and contract manufacturing organizations (CMOs).

The following are some of the reasons why outsourcing is becoming more and more prevalent in pharmaceutical development (1):

increased flexibility to pivot research and development focus

reduced personnel and facilities costs to companies

leveraging of CRO’s specific technologies and expertise in study design and execution, project management, and quality assurance

non-bias and independent validation of initial results obtained at companies’ facilities.

Preclinical CROs fill this need as they often provide these specialized platforms and expertise to assist companies to successfully push their products through the R&D to IND process, ultimately resulting in clinical testing required for entry into the market. From 

, and analytical/bioanalytical services, subcontracted organizations can provide turnkey solutions to these companies that may lack internal facilities, instrumentation, knowledge, and quality systems to successfully execute the necessary studies to assess their target compound’s efficacy and toxicity. For instance, the costs to construct, manage, and maintain 

facilities may be prohibitive for companies, especially for small start-ups with limited capital. Even larger companies, which have traditionally maintained these types of capabilities internally, are downsizing their internal 

capabilities due to the ever-increasing regulatory burden and the ever-increasing costs required to staff and maintain these facilities. A CRO with this specific expertise and appropriate facilities can easily execute these types of studies at relatively low cost with a well-trained professional team overseeing all aspects of the study, ensuring a high-quality efficacious project.

Daniel Radiloff, PhD, is director of Business Development, Pacific BioLabs.

When referring to this article, please cite it as Radiloff, D. Leveraging Blow-Fill-Seal Technology for Biologic Delivery. 

Outsourcing

The need for preclinical testing expertise is growing as molecular complexity increases.

Navigating the Preclinical CRO Outsourcing Process

The demand for blow-fill-seal (BFS) technology has significantly increased in recent years because of the rising demand for biologic-based drug products and vaccines. Valued at $2.8 billion in 2022, the BFS technology market is predicted to grow at a compound annual growth rate of 9% until 2031, to reach $6.2 billion (1).

Created through automated manufacture, BFS is being explored for unit dose containers for vaccines and other biologic products. This BFS process can positively impact the overall supply chain, lowering manufacturing costs and enabling treatment for populations in lower-income regions.

BFS technology is a form of advanced aseptic manufacturing in which a container for a drug formulation is formed, filled, and sealed in a continuous, automated system. To create the aseptic container, manufacturers continuously melt polymer granules to extrude a sterile, formable polymer parison into a mold. Sterile air is used to blow-mold the material into a container, forcing the polymer to take the shape of the mold and create a hollow space within. This container is filled with a drug formulation before being sealed tightly, traditionally through the application of both heat and pressure to the open end of the vessel.

All containers have features that can make them more or less suitable for a particular project. BFS is no different, offering features that make it an increasingly attractive option for pharmaceutical companies developing or manufacturing sterile liquids, including injectables. For example, BFS containers:

Maintain high sterility and particulate contamination integrity while optimizing production line efficiency. BFS formation, filling, and sealing can be easily incorporated into a sterile manufacturing process, similar to those required for the production of injectable formulations. The process is highly automated, limiting the risk of microbial or particulate contamination from human intervention. The container only needs to be formed immediately before use and is sealed as soon as it is filled, with no need for an additional manufacturing stage for a closure to be applied. This helps simplify and shorten the production line further while maintaining optimum integrity against contamination.

Support cost-effective clinical and commercial manufacturing at any scale. The process of forming the containers only as they are needed supports high-volume commercial filling, as well as small-batch finishing for clinical or small-scale commercial needs. BFS removes the need for pre-treatment of the container and a separate set of equipment for applying closures, streamlining the filling process. Logistics is reduced considering pallets and materials to move vials from suppliers to fill/finish provider and then into the market.

Offer design flexibility. BFS containers can be made in a uniquely wide range of shapes and sizes, enabling them to easily meet the specific dose or even administration needs of individual drug products. Containers shape can be adapted to consumer needs and by simply having the right molding cavity to manufacture the final container.

Eliminate the need for preservatives. BFS containers can be specifically designed for single-use—with no need for a reclosable closure. For unidose formats relying on BFS containers, there is no need to use preservatives that could affect the drug product’s quality or safety. Mitigating the need for preservatives could also help to reduce the development time frame for the drug formulation.

Reduce the risk of drug waste. As the BFS container is made of plastic rather than glass, there is less risk of breakage during transport, helping to reduce waste from damaged dose units. BFS containers that are designed for unidose applications can minimize waste from expired formulations that might be left in multi-use containers.

Vincenza Pironti, PhD,is strategic marketing director at Recipharm.

When referring to this article, please cite it as Pironti, V. Leveraging Blow-Fill-Seal Technology for Biologic Delivery. 

Manufacturing

The rising demand for biologics and technological innovations are driving blow-fill-seal capacity, harnessing manufacturing efficiency, and benefitting patients.

Partnerships for Outsourcing, May 2024 eBook

Ensuring Quality in Contracted Support

How to Evaluate a CDMO’s Commitment to Quality

Navigating the Preclinical CRO Outsourcing Process

Leveraging Blow-Fill-Seal Technology for Biologic Delivery